We have utilized human thyroid cancer cell lines that are characterized by different metabolic profile - utilizing predominantly oxidative phosphorylation for the energy production or relying on glycolysis. We have found that treatment with metformin is associated with a change in a metabolic phenotype of thyroid cancer cells in vitro. Therapy with metformin is associated with a significant reduction of oxidative phosphorylation and reprogramming of cancer cells metabolism towards glycolysis. We have found a certain molecular signature and metabolic phenotype of thyroid cancer cells, which are associated with growth inhibitory effects of metformin in vitro and in vivo in a metastatic mouse model.